The invention relates to “active implantable medical devices” as defined by the Directive 90/385/EEC of 20 Jun. 1990 of the Council of the European Communities, namely implants for delivering stimulation therapy to the vagus nerve or to one of its branches, known as VNS (Vagus Nerve Stimulation) therapy.
It more particularly relates to the use of such therapies in patients at risk of heart failure.
VNS acts on cardiovascular function by reducing heart rate and myocardial contractility with decreased duration of diastole, which may help reduce the development of cardiac remodeling that may lead to heart failure.
In general, patients with risk of heart failure have an increased heart rate (HR) compared to healthy patients, which may require taking drugs such as beta blockers to reduce the heart rate and thus improve the patient prognosis.
A high heart rate is often a predictor of increased mortality in the general population, with a higher risk of stroke, this risk being typically increased by 3% for each increase of one beat per minute (bpm) of the average heart rate.
It is also known that VNS therapies have a direct effect on heart rate by acting on the parasympathetic balance. This heart rate reduction effect occurs:
In the short term, by a change in the SympathoVagal Balance (SVB) leading to a restoration of a heart rate well suited to the patient's current activity, and
In the long term with beneficial effects after months of VNS therapy even if the instant restoration of SVB balance is not reached.
One of the difficulties of VNS therapy lies in the adjustment of the stimulation parameters.
In the short term, when dynamic change of the stimulation, depending on the patient's instantaneous activity, is required, this change is made from a variety of parameters representative of the patient's current condition such as heart rate, metabolic needs, etc.
VNS therapy is then automatically controlled or modulated as a function of the level of detected current activity, for example by selection between a plurality of energy levels of VNS stimulation pulses.
However, when adjustment of the VNS therapy parameters is desirable for getting a beneficial effect in the long term, this adjustment is generally left to the discretion of the physician, who does it more or less empirically.
Furthermore, adjustment or readjustment of these parameters by the physician is only performed during monitoring visits, even though the patient's condition can change over time, due to VNS therapy or independently thereof, and the initial setup does not reflect these changes.
Thus, techniques such as those described for example by US 2012/0095530 A1 (U.S. Pat. No. 8,433,419 B2) are used to adapt the VNS therapy to the patient's activity level. The activity level can be evaluated by an appropriate sensor such as an accelerometer integrated into the housing of the implanted VNS pulse generator. The sensor signal is compared to a set of predefined thresholds, and the VNS stimulation parameters, mainly the stimulation energy, are selectively adjusted according to the crossed thresholds, especially to adapt the therapy by allowing the expression of an increased heart rate correlated to the effort.
However, with this device the modulation of VNS therapy does not take into account the medium and/or long-term evolution (e.g. one day to another and/or over a period of several days or weeks) of the pathology of the patient, in case of worsening as well as in case of improving of his/her condition.
Other similar techniques have been proposed, but it is always to make a dynamic adaptation of the VNS therapy by rate response over a signal from an activity sensor or other sensor of a physiological parameter of the patient. This dynamically improves the instant effectiveness of the VNS therapy but without taking into account changes in the long term of the patient's condition.
WO 2014/074523 A1 discloses a VNS stimulator for storing various physiological and stimulation data, and incorporating adaptation functions in the time of VNS stimulation, controlled for example by monitoring arrhythmias induced by therapy, or implementing a weighting of physiological events stored so as to give greater importance to recent events compared to the oldest ones.